Department of Hematology, Fujita Health University, 98 Dengakugakubo, Toyoake, Aichi, 470-1192, Japan.
National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Int J Hematol. 2018 Aug;108(2):208-212. doi: 10.1007/s12185-017-2387-x. Epub 2017 Dec 20.
Variant chromosomal translocations associated with t(8;21) are observed in 3-4% of acute myeloid leukemia (AML) cases with a RUNX1-RUNX1T1 fusion gene. However, the molecular events that occur in variants of t(8;21) are not well characterized. In the present study, we report genetic features of a variant three-way translocation of t(8;12;21)(q22;p11;q22) in a patient with AML. In this patient, leukemia cells lacked azurophilic granules, which does not correspond with the classic features of t(8;21). RNA-seq analysis revealed that TM7SF3 at 12p11 was fused to VPS13B at 8q22 and VPS13B to RUNX1, in addition to RUNX1-RUNX1T1. VPS13B was located near RUNX1T1 and both were localized at the same chromosomal bands. The reading frames of TM7SF3 and VPS13B did not match to those of VPS13B and RUNX1, respectively. Disruption of VPS13B causes Cohen syndrome, which presents intermittent neutropenia with a left-shifted granulopoiesis in the bone marrow. Disruption of VPS13B may thus cause the unusual features of RUNX1-RUNX1T1 leukemia. Our case indicates that rearrangement of VPS13B may be additional genetic events in variant t(8;21).
与 RUNX1-RUNX1T1 融合基因相关的 8;21 号染色体易位变体在 3-4%的急性髓系白血病（AML）病例中观察到。然而，变体 t(8;21)中发生的分子事件尚未得到很好的描述。在本研究中，我们报告了一例 AML 中变体三向易位 t(8;12;21)(q22;p11;q22)的遗传特征。在该患者中，白血病细胞缺乏嗜天青颗粒，这与经典的 t(8;21)特征不符。RNA-seq 分析显示，12p11 处的 TM7SF3 与 8q22 处的 VPS13B 以及 VPS13B 与 RUNX1 融合，除了 RUNX1-RUNX1T1 之外。VPS13B 位于 RUNX1T1 附近，两者均位于相同的染色体带。TM7SF3 和 VPS13B 的阅读框与 VPS13B 和 RUNX1 的阅读框不匹配。VPS13B 的破坏会导致 Cohen 综合征，其特征为骨髓中粒细胞生成呈间歇性中性粒细胞减少和左移。VPS13B 的破坏可能导致 RUNX1-RUNX1T1 白血病的异常特征。我们的病例表明，VPS13B 的重排可能是变体 t(8;21)中的其他遗传事件。
